4.5 Field Safety 

1. Overview

Field safety studies are one component of the safety evaluation required for a product prior to 

licensure. Field safety trials (FST) according to Veterinary Services Memorandum (VSM 800.204 )

are typically uncontrolled, loosely exploratory trials conducted under typical field husbandry 

(i.e., intended use) conditions. The objective of a FST is to assess the safety of the product in its 

target population under the conditions of its intended use. It is intended to detect the types of 

adverse events which may occur with sufficient frequency to be seen in a trial of this scale. The 

FST is an essential clinical component of the prelicense process, supplementing smaller 

preclinical experimental studies, but it does not replace ongoing post-marketing surveillance.

While FSTs conducted as per VSM 800.204 satisfy the safety requirements for most products, there 

are times when other types of more rigorous field safety studies may be necessary. Such studies 

generally need the usual features of any designed study and should follow the guidance for study 

design in documents such as VSM 800.200 and VSM 800.202. For example, most studies of 

reproductive performance with PRRS MLV vaccines have been well designed and followed a 

specific analysis.

2. Related Documents

• VSM 800.50: Basic License Requirements and Guidelines for Submission of Materials 

in Support of Licensure 

• VSM 800.67--Shipment of Experimental Veterinary Biological Products

• VSM 800.204--General Licensing Considerations: Field Safety Studies 

• VSM 800.211 Licensing Considerations: Vaccine Claims for Protection of the Fetus 

Against Bovine Virus Diarrhea Virus 

3. Procedures

3.1 Permission to conduct a field study must be obtained from the Center for Veterinary 

Biologics. See the Reviewer Manual Chapter titled “Shipping Experimental Product under 

9CFR 103.3,” and VS Memoranda 800.50 and 800.67, for details. 

3.2 Applicants are strongly encouraged to submit a detailed protocol for review and 

comment prior to conducting a study. See the Reviewer Manual chapter titled “Study 

Protocols” for additional detail. 

3.3 If the product to be tested is biotechnology derived, a risk assessment must be completed 

prior to authorizing a field release. The CVB also may elect to conduct a risk assessment on 

certain conventional modified live products; contact the Risk Manager in these cases. For 

certain types of products, a notice of intent to conduct the study must be published in the 
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Federal Register. See VS Memoranda 800.50 and 800.205, and the Reviewer Manual 

chapter titled “Summary Information Format (SIF) and Risk Analyses,” for additional detail.

3.4 Field safety studies should be authorized only after product efficacy has been adequately 

demonstrated. Exceptions must be cleared by the Section Leader. 

3.4.1 If a field safety study is conducted prior to acceptance of pivotal efficacy data (or 

“reasonable expectation” efficacy data for conditional licenses), the firm must provide 

clearly worded efficacy disclaimers to each participating animal owner (see Section 4.4 

for details). In such cases, the reviewer must notify the firm that the study is being 

undertaken at their own risk; should the product subsequently be deemed insufficiently 

efficacious, the firm is required to notify each participating animal owner.

3.4.2 Field safety studies are never to be authorized prior to adequate demonstration of 

efficacy for rabies vaccines.

3.4.3 When the product contains live organisms, studies demonstrating a lack of 

reversion to virulence (aka backpassage) also should be completed prior to authorizing a 

field study. See VS Memorandum 800.201 for details on backpassage studies.

3.4.4 Acceptable inactivation (including inactivation kinetics) must be demonstrated for 

killed products prior to authorizing field studies. 

3.4.5 Serials used in field safety studies must be tested according to Section V of the 

Outline of Production, using assays acceptable to the CVB. The firm conducts the study 

at its own risk if they use serials in the study that have not yet been tested with an 

approved potency test. Even in such cases, some type of potency testing should be 

completed prior to study initiation. 

3.4.6 Firms often use prelicense serials in field safety studies, but this is not a 

requirement. If they do not use prelicense serials, the serials still must be typical of the 

manufacturing process described in the Outline of Production, and they should be 

submitted to the CVB for confirmatory testing to verify potency.

3.4.7 Generally, studies in broiler birds are followed to slaughter with slaughter data on 

condemnations reported. Depending on the disease, these studies may serve as field 

safety studies, as well as provide an indicator of field efficacy If a 

disease lesion (preventable by the vaccine) would cause condemnation, it should be 

reported separately from the total number of carcasses condemned (for example E. coli 

product/air sacculitis condemnations or Marek’s product/tumor formation). Layer birds 

are followed for a similar time period as broiler birds but no condemnation data are 

required. 


Field Safety 5 of 6 

cooperator from each lay participant (i.e., Don’t rely on passive submission of completed 

forms, assuming everything is OK if the owner doesn’t return the forms.)

4.3.5 It is common for the reported adverse event rate to vary substantially among 

cooperators. In many cases, this is due to differences in reporting. (Example: One 

cooperator may be very diligent in reporting every small, transient swelling. Another 

may consider such swellings to be a “normal” consequence of vaccination and will not 

note anything on the data form.) 

This variation can be minimized by adequate training of all cooperators. Firms are 

responsible for clarifying to cooperators that ALL sequelae, regardless of magnitude or 

duration, should be reported. The clinical relevance of the events will be determined 

during data analysis; data should not be censored at the cooperator level. 

Firms should not pool data from different sites in the final report. If there are material 

site differences, adverse event rates should be described as a range of the individual site 

values rather than an average value.

4.4 Informed consent forms: Animal owners should always be notified that an experimental 

product is being used; to this end, most firms will provide some kind of informed consent 

form. In special situations where the field safety study is being performed before pivotal 

efficacy has been demonstrated (see Section 3.4), a specific informed consent form is 

required. Similarly, if confirmatory testing of prelicensing serials by the CVB is not yet 

completed, specific pre-approved disclaimers may be required. Firms should provide a copy 

of the informed consent form for CVB review with the study protocol, and it is the 

responsibility of the reviewer to ensure that the form adequately and prominently discloses 

the efficacy status of the product. (Avoid forms that attempt to downplay the significance of 

the undetermined efficacy and/or hide this disclosure in small print.) 

4.5 The use of beta-adrenergic agonists in feedlot cattle or feeder pigs concurrent with the 

vaccination-observation period of the study: Beta agonists such as OptaflexxTM, PayLeanTM, 

and ZilmaxTM are sometimes used in feedlot cattle and feeder pigs to increase lean slaughter 

weight; these products are typically used the last 30 days of feeding. The CVB will not 

accept data from field safety studies when these drugs are used concurrently with vaccination

as use of these drugs can mask and/or cause adverse effects, and normally are not 

administered at the same time as vaccination. 

4.6 Inconsistent test results (between the firm and confirmatory testing at the CVB): If 

results obtained during confirmatory testing call product safety into question, the CVB 

laboratory may conduct small scale studies with prelicensing serials to further evaluate 

product safety prior to authorization of field safety studies. 

5. Review of Field Safety Study Reports

5.1 Statistics Review